Neuromuscular junctions in Drosophila larvae are very accessible to neurophysiology, because the preparation is thin and visible with Nomarski optics, each muscle fiber is essentially isopotential, and the nerve terminals are readily accessible to experimental manipulations. The quantal nature of transmitter release, the ionic basis of the membrane resting potential and the excitatory junctional potential, as well as postsynaptic action of L-glutamate, have been worked out in detail. Since single-gene mutations affecting the synapse can be isolated, one can combine genetics, electrophysiology and biochemistry in studying the synapse. So far three mutations affecting neuromuscular transmission have been found, mapped genetically and cytologically, and studied to some detail electrophysiologically. These studies revealed the role of internal sodium accumulation in long-term facilitation, as well as the possible chemical lesions caused by these mutations. More mutations affecting the synapse will be studied with the hope of revealing hitherto unsuspected processes underlying synaptic transmission or changes of synaptic efficacy. As to those mutants that have been studied previously, biochemical analysis will be performed to test whether they have the chemical lesions predicted from the results of electrophysiological experiments. Some of the mutants may also be used in probing developmental problems such as the role of neural activity during the wiring of the nervous system, or the possible interaction between nerve and muscle in the pattern formation in either tissue.